Secondary Metabolites with Antifungal Activities from Mangrove Derived Fungus Monascus purpureus WMD2424.

The mold Monascus, also called red yeast rice, anka, or koji, has been used as the natural food coloring agent and food additives for more than 1000 years in Asian countries. It has also been used in Chinese herbology and traditional Chinese medicine due to its easing digestion and antiseptic effects. However, under different culture conditions, the ingredients in Monascus-fermented products may be changed. Therefore, an in-depth understanding of the ingredients, as well as the bioactivities of Monascus-derived natural products, is important. Here, through the thorough investigation into the chemical constituents of M. purpureus wmd2424, five previously undescribed compounds, monascuspurins A-E (1-5), were isolated from the EtOAc extract of mangrove-derived fungus Monascus purpureus wmd2424 cultured in RGY medium. All the constituents were confirmed via HRESIMS and 1D- and 2D-NMR spectroscopy. Their antifungal activity was also evaluated. Our results showed that four constituents (compounds 3-5) possessed mild antifungal activity against Aspergillus niger, Penicillium italicum, Candida albicans, and Saccharomyces cerevisiae. It is worth mentioning that the chemical composition of the type strain Monascus purpureus wmd2424 has never been studied.

Two new chromones and a new coumarin from the fruit of Cnidium monnieri (L.) Cusson.

Two new chromones named cnidimol G (1) and cnidimol H (2), one new coumarin, 7-methoxy-8-(3-methoxy-3-methyl-2-oxobutyl)coumarin (3), and twenty known compounds were isolated from MeOH extract of the fruit of Cnidium monnieri (L.) Cusson. The structures of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, HRESIMS, IR and UV. Anti-inflammatory activity of the selected isolated compounds were evaluated. Compounds 1 and 8 exhibited inhibitory activities against nitric oxide production.

Undescribed alkyne-geranylcyclohexenetriols from the endophyte Diaporthe caulivora 09F0132 and their anti-melanogenic activity.

To explore valuable endophytic fungus from Formosan Lauraceous plants as natural medicinal products, the fungus, Diaporthe caulivora isolated from leaves of Neolitsea daibuensis, was investigated. Through a thorough investigation of the ethanolic extract of the solid fermentation of D. caulivora 09F0132, six undescribed alkyne-geranylcyclohexenetriols, caulivotrioloxins A-F, one undescribed trichopyrone, diapopyrone, two undescribed sesquiterpenes, caulibysins A-B, one compound firstly isolated from the natural source, 3-O-desmethyl phomentrioloxin, and eight known compounds have been successfully identified. The absolute configuration of caulibysin A was confirmed by single-crystal X-ray diffraction, and those of (3R,8S)-5,7-dihydroxy-3-(1-hydroxyethyl)phthalide and (3S,8S)-5,7-dihydroxy-3-(1-hydroxyethyl)phthalide were determined by circular dichroism (CD) spectra. Among the isolated compounds, caulivotrioloxin A concentration-dependently decreased the cellular melanin contents and tyrosinase activities in mouse melanoma B16-F10 cells, suggesting the anti-melanogenic potentials. The anti-melanogenic effects of caulivotrioloxin A involved the decrease in the protein expressions of melanogenic enzymes, including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Taken together, these results suggested that the isolates from D. caulivora could be served as natural melanogenesis inhibitors for cosmeceutical applications.

Secondary Metabolites with Antimicrobial Activities from Chamaecyparis obtusa var. formosana.

Seven new compounds, including one dimer novel skeleton, chamaecyformosanin A (1); three diterpenes, chamaecyformosanins B-D (2-4); one sesquiterpene, chamaecyformosanin E (5); and two monoterpenes, chamaecyformosanins F and G (6 and 7) were isolated from the methanol extract of the bark of Chamaecyparis obtusa var. formosana. Their structures were established by the mean of spectroscopic analysis and the comparison of NMR data with those of known analogues. Their structures were elucidated on the basis of physicochemical evidence, in-depth NMR spectroscopic analysis, and high-resolution mass spectrometry. Furthermore, the isolated compounds were subjected to an evaluation of their antimicrobial activity. Metabolites 1, 3, and 4 present antibacterial activities. It is worth mentioning that the chemical composition of the bark of C. obtusa var. formosana has never been studied in the past. This is the first time the barks from C. obtusa var. formosana were studied and two new skeleton compounds, 1 and 7, were obtained.

Novel Antifungal Dimers from the Roots of Taiwania cryptomerioides.

Five new dimer compounds, namely Taiwaniacryptodimers A-E (1-5), were isolated from the methanol extract of the roots of Taiwania cryptomerioides. Their structures were established by mean of spectroscopic analysis and comparison of NMR data with those of known analogues. Their antifungal activities were also evaluated. Our results indicated that metabolites 1, 2, 4, and 5 displayed moderate antifungal activities against Aspergillus niger, Penicillium italicum, Candida albicans, and Saccharomyces cerevisiae.

Different types of components obtained from Monascus purpureus with neuroprotective and anti-inflammatory potentials.

The mold Monascus has been used as a natural food coloring agent and food additive for more than 1000 years in Asian countries. In Chinese herbology, it was also used for easing digestion and antiseptic effects. Through a thorough investigation of a citrinin-free strain: M. purpureus BCRC 38110, four azaphilones, three benzenoids, one benzofuranone, one 5',6'-dihydrospiro[isochromane-1,2'-pyran]-4'(3'H)-one derivative, two steroids, and six tetralones have been successfully identified. Among them, monapyridine A (1), monatetralones A-E (2-6), and monabenzofuranone (7) were first reported. Their structures were characterized by 1D and 2D NMR, UV, IR, and HRESIMS analyses. With a series of bioactivity screening, monascuspirolide B (14) and ergosterol peroxide (16) exhibited concentration-dependent attenuation of the paclitaxel-induced neurite damage of mouse dorsal root ganglion neurons. The interleukin (IL)-1ß-induced release of inflammatory cytokines IL-8 and tumor necrosis factor (TNF)-α in human chondrosarcoma cells was inhibited by monapurpureusone (8) and monascuspirolide B (14). Altogether, M. purpureus BCRC 38110 possessed potentials as natural therapeutics against inflammatory osteoarthritis and paclitaxel-induced neurotoxicity.

Two new diprenylated flavanones from Derris laxiflora Benth.

Phytochemical reinvestigation on the whole plants of Derris laxiflora Benth. afforded two new diprenylated flavanones, derriflavanones B and C (1-2), together with thirty-two known compounds, including sixteen flavonoids (3-18), eleven aromatic compounds (19-29), and five chlorophylls (30-34). All known compounds were first isolated from this plant. The structures of these compounds were determined by analysis of the NMR spectroscopy, mass data, IR spectra, UV spectra, optical rotation and by comparison with literature data.

New Benzenoid Derivatives and Other Constituents from Lawsonia inermis with Inhibitory Activity against NO Production.

Three new benzenoid derivatives, lawsoinermone (1), inermidioic acid (2), and inermic acid (3) have been isolated from the aerial part of Lawsonia inermis, together with 11 known compounds (4-14). The structures of three new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4-6, 13 and 14 were evaluated for inhibition of nitric oxide production in LPS-stimulated product of nitrite in RAW 264.7 cells with IC50 values of 6.12, 16.43, 18.98, 9.30, 9.30 and 14.90 µg/mL, respectively.

Phytochemical investigation of Annulohypoxylon ilanense, an endophytic fungus derived from Cinnamomum species.

Cultivation of the fungal strain Annulohypoxylon ilanense, an endophytic fungus isolated from the wood of medicinal plant Cinnamomum species, resulted in the isolation of one new furanoid derivative, ilanefuranone (1), one new pyrrole alkaloid, ilanepyrrolal (2), and one new biarylpropanoid derivative, ilanenoid (3), together with 22 known compounds, of which one α-tetralone analog, (-)-(4R)-3,4-dihydro-4,6-dihydroxynaphthalen-1(2H)-one (4) was isolated for the first time from a natural source. The structures were elucidated on the basis of physicochemical evidence, in-depth NMR spectroscopic analysis, and high-resolution mass spectrometry, and the antimycobacterial activities were also evaluated.

Analysis of Taiwan patents for the medicinal mushroom "Niu-Chang- Chih".

"Niu-Chang-Chih" (Antrodia cinnanomea) is a medicinal mushroom that has only been collected from the aromatic tree, Cinnamomum kanehirai, which is native to Taiwan. A total of 105 Taiwan patent applications and patents for "Niu-Chang-Chih" were collected and analyzed. Patent applications and granted patents claiming newly identified functional components from "Niu-Chang-Chih," biologically pure cultures of the mushroom strain, and cultivation of "Niu-Chang-Chih" were examined. Several applications and patents claim identified active compounds from "Niu-Chang- Chih," which provide better patent protection. These newly identified functional compounds include cyclohexanones, maleic and succinic acid derivatives, labdane diterpenoids, and benzenoids. Newly identified functional proteins include a glutathione-dependent formaldehyde dehydrogenase (GFD), a glycoprotein named ACA1, and a laccase. Newly identified functional polysaccharides include ACP1, ACP2, and ACP3. The number of patents for newly identified compounds and their uses are expected to continue growing.

Monascuspiloin enhances the radiation sensitivity of human prostate cancer cells by stimulating endoplasmic reticulum stress and inducing autophagy.

Prostate cancer is a very common cancer among males. Traditional treatments for prostate cancer have limited efficacy; therefore, new therapeutic strategies and/or new adjuvant drugs must be explored. Red yeast rice (RYR) is a traditional food spice made in Asia by fermenting white rice with Monascus purpureus Went yeast. Accumulating evidence indicates that RYR has antitumor activity. In this study, PC-3 cells (human prostate cancer cells) were used to investigate the anti-cancer effects of ionizing radiation (IR) combined with monascuspiloin (MP, a yellow pigment isolated from Monascus pilosus M93-fermented rice) and to determine the underlying mechanisms of these effects in vitro and in vivo. We found that IR combined with MP showed increased therapeutic efficacy when compared with either treatment alone in PC-3 cells. In addition, the combined treatment enhanced DNA damage and endoplasmic reticulum (ER) stress. The combined treatment induced primarily autophagy in PC-3 cells, and the cell death that was induced by the combined treatment was chiefly the result of inhibition of the Akt/mTOR signaling pathways. In an in vivo study, the combination treatment showed greater anti-tumor growth effects. These novel findings suggest that the combined treatment could be a potential therapeutic strategy for prostate cancer.

Antioxidant activities of extracts and metabolites isolated from the fungus Antrodia cinnamomea.

Three different solvent partitions (n-hexane, ethyl acetate [EtOAc] and n-BuOH) of the culture broth from Antrodia cinnamomea were assayed with two different radical scavenging methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and superoxide radical scavenging (SOD) assay. The EtOAc layer exhibited the best antioxidant activity. Two major antioxidant metabolites were isolated from the active EtOAc layer. The antioxidant activities of compounds 1-6 were further evaluated by DPPH, SOD and trolox equivalent antioxidant capacity (TEAC) assays. Compounds 3 and 5 showed stronger free radical scavenging than the reference BHA, ED50 = 1.36 and 34.24 µM. Compound 5 displayed moderate SOD activity (ED50 = 310.0 µM), and its antioxidant capacity of TEAC value was 2.2 mM trolox equivalency.

Isolation and structure determination of one new metabolite isolated from the red fermented rice of Monascus purpureus.

The n-BuOH-soluble portion of the 95% EtOH extract of red fermented rice fermented with the yellow mutant of the fungus Monascus purpureus BCRC 38113 (Monascaceae) led to the isolation of one new pyran-2-one derivative, namely peroxymonascuspyrone (1), along with nine known compounds, monasfluore A (2), monasfluore B (3), 3-epi-betulinic acid (4), 3-epi-betulinic acid acetate (5), alpha-tocospiro A (6), friedelan-3-one (7), alpha-cadinol (8), anticopalol (9), and spathulenol (10). Interestingly, this is the first report of a naturally occurring pyran-2-one skeleton isolated from Monascus sp. Their structures and relative configurations were elucidated by spectroscopic methods, including 1D- and 2D-NMR ((1)H,(1)H-COSY, HMQC, HMBC and NOESY), as well as low- and high-resolution mass spectrometric analyses. In addition, cytotoxicities against MCF-7, NCI-H460 and SF-268 cancer cell lines were measured in vitro; the results revealed that these metabolites have no cytotoxicity against the selected tumour cells.

Flavanone and diphenylpropane glycosides and glycosidic acyl esters from Viscum articulatum.

Seven new compounds including three flavanone glycosides, visartisides A-C (1-3), three glycoside acyl esters, visartisides D-F (4-6), and one diphenylpropane glycoside, (4'-hydroxy-2',3',6',3''-tetramethoxy-1,3-diphenylpropane)-4''-O-beta-d-glucopyranoside (7), along with four known flavanone glycosides (8-11) were isolated from the leaves and stems of Viscum articulatum. The structure elucidation of 1-7 was based on spectroscopic data analysis. Biological evaluation showed that 1, 2, and 10 exhibited antioxidant activity using a DPPH method and that compounds 1, 3, and 11 were active in a lipopolysaccharide-induced nitric oxide assay.

Labdane diterpenoid glycosides from Alpinia densespicata and their nitric oxide inhibitory activities in macrophages.

Four new labdane diterpene glycosides (1-4) named alpindenosides A, B, C, and D, two new norditerpene glycosides (5, 6) named noralpindenosides A and B, and three known flavonoid glycosides (7-9) have been isolated from the stems of Alpinia densespicata. Structural elucidation of compounds 1-6 was based on spectroscopic data. Compounds 1-9 all exhibited moderate NO inhibitory activities, whereas they were noncytotoxic at 20 microM against several human tumor cell lines.

Antihepatitis activity (anti-HBsAg and anti-HBeAg) of C19 homolignans and six novel C18 dibenzocyclooctadiene lignans from Kadsura japonica.

Bioassay-directed fractionation of the EtOAc extract of Kadsura japonica has led to the isolation of six new C18 dibenzocyclooctadiene lignans, schizanrins I, J, K, L, M, N, along with four known C19 homolignans, taiwanschirins A, B, C, and heteroclitin F. The elucidations of the new structures were based on spectral analysis. Bioassay evaluation against human type B hepatitis revealed that taiwanschirins A and B showed strong activity for anti-HBsAg and a medium effect for anti-HBeAg at 25 microg/mL (12.9 and 11.9 microM for taiwanschirins A and B, respectively).

Two novel sesquiterpene lactones, cytotoxic vernolide-A and -B, from Vernonia cinerea.

Bioassay-directed fractionation of an ethanolic extract of stems of Vernonia cinerea has resulted in the isolation of two novel sesquiterpene lactones, vernolide-A and -B. Their structures were elucidated on the basis of spectroscopic analysis. Biological evaluation showed that vernolide-A demonstrated potent cytotoxicity against human KB, DLD-1, NCI-661, and Hela tumor cell lines (ED(50)=0.02, 0.05, 0.53, 0.04 microg/ml for KB, DLD-1, NCI-661, and Hela, respectively); vernolide-B had marginal cytoxicity (ED(50)=3.78, 5.88, 6.42 microg/ml for KB, NCI-661, and Hela, respectively).